Gavin Chit Tsui

Rhodium(I)-catalyzed addition of arylboronic acids to (benzyl-/arylsulfonyl)acetonitriles: efficient synthesis of (Z)-β-sulfonylvinylamines and β-keto sulfones.

An efficient rhodium(I)-catalyzed addition of arylboronic acids to (benzyl-/arylsulfonyl)acetonitrile is described. Novel β-sulfonylvinylamine products are formed in a stereoselective fashion (Z-alkene). Upon hydrolysis, useful β-keto sulfones are obtained with a broad scope of aryl and sulfonyl substituents.

Rhodium(I)‐Catalyzed Domino Asymmetric Ring Opening/Enantioselective Isomerization of Oxabicyclic Alkenes with Water

Rhodium(I)-catalyzed asymmetric ring-opening (ARO) reaction of strained bicyclic alkenes has been demonstrated as a highly efficient and enantioselective process for generating a functionalized dihydronaphthalene core. Our group has previously reported that chiral Rh complexes catalyze ring opening of oxaand azabicyclic alkenes with soft nucleophiles such as alcohols, phenols, thiols, amines, anilines, malonates and carboxylates in high yield and enantioselectivity. The products are generated by an SN2’ nucleophilic displacement of the bridgehead leaving group with inversion to give the 1,2trans product as a single regioand diastereomer. This method has been recently demonstrated as a viable strategy for synthesizing bioactive aminotetralins rotigotine and (S)-8OH-DPAT. Although various heteroatom nucleophiles have been employed in ARO, the use of water—the simplest nucleophile—has not been demonstrated. Based on previous studies, water-induced ARO of oxabenzonorbornadiene 1a should yield chiral trans-1,2-diol 2a. Instead, we isolated the unexpected 2-hydroxy-1-tetralone product 3a exclusively in the presence of catalytic [Rh(cod)Cl]2/(R,S)-PPF-PtBu2 (cod = cyclooctadiene) in aqueous THF (Scheme 1). Reaction at 25 8C afforded enantio-enriched 3a (enantiomeric ratio, e.r. = 33:67), a higher reaction temperature (50 or 80 8C) caused a significant decrease in enantioselectivity. To the best of our knowledge, the formation of tetralone products such as 3a is unprecedented in ARO reactions. We subsequently investigated the effects of ligand, catalyst loading, concentration, and reaction temperature (Table 1). No reaction took place without added ligand (entry 1). Reaction at 25 8C (0.2m concentration) with 5 mol% [Rh(cod)Cl]2 and 10 mol % (R,S)-PPF-PtBu2 gave tetralone product 3 a in 79 % yield (entry 2, cf. Scheme 1). As the catalyst loading was decreased to 2 mol %, we obtained a mixture of diol 2 a (major product) and tetralone 3a

One-Pot Synthesis of Chiral Dihydrobenzofuran Framework via Rh/Pd Catalysis

A one-pot synthesis of the chiral dihydrobenzofuran framework is described. The method utilizes Rh-catalyzed asymmetric ring opening (ARO) and Pd-catalyzed C-O coupling to furnish the product in excellent enantioselectivity without isolation of intermediates. Systematic metal-ligand studies were carried out to investigate the compatibility of each catalytic system using product enantiopurity as an indicator.

Expedient Synthesis of Chiral Oxazolidinone Scaffolds via Rhodium-Catalyzed Asymmetric Ring-Opening with Sodium Cyanate

A method for synthesizing chiral oxazolidinone scaffolds from readily available oxabicyclic alkenes is described. The reaction utilizes a domino sequence of Rh(I)-catalyzed asymmetric ring-opening (ARO) with sodium cyanate as a novel nucleophile followed by intramolecular cyclization to generate oxazolidinone products in excellent enantioselectivities (trans stereochemistry).

Regioselective Rhodium(I)-Catalyzed Hydroarylation of Protected Allylic Amines with Arylboronic Acids

A novel regioselective rhodium(I)-catalyzed hydroarylation of unactivated alkenes with arylboronic acids is described. The catalytic system employs [Rh(COD)OH](2) and BINAP to effect the addition of various arylboronic acids to protected allylic amines. The regioselectivity was found to be highly dependent on the protecting group, favoring the linear addition product with up to 92% yield and >20:1 regioselectivity.

Iron-Catalyzed Cross-Coupling Reactions between a Bicyclic Alkenyl Triflate and Grignard Reagents

Fe-catalyzed cross-coupling reactions between a bicyclic alkenyl triflate and Grignard reagents were investigated. Under the optimized reaction conditions, various 2-substituted bicyclic alkenes were synthesized in moderate to excellent yields (52-93%). This method provided an efficient route for the synthesis of 2-substituted bicyclic alkenes with secondary alkyl groups which cannot be synthesized using previous methods such as Pd-catalyzed coupling reactions and lithium-halide exchange reactions.

Fluoroform-Derived CuCF3 for Trifluoromethylation of Terminal and TMS-Protected Alkynes

An efficient trifluoromethylation reaction of alkynes using a fluoroform-derived CuCF3 reagent is described. The CF3 source is the inexpensive industrial waste fluoroform (CF3H). The air-stable CuCF3 reagent can be prepared in large quantities and is convenient to use. Synthetically useful trifluoromethylated alkynes containing a wide range of functional groups were successfully synthesized under mild conditions. Both terminal and TMS-protected alkynes gave the products in one step. The beneficial effect of a diamine ligand tetramethylethylenediamine (TMEDA) with the fluoroform-derived CuCF3 reagent was also demonstrated.

Hydroxytrifluoromethylation of Alkenes Using Fluoroform-Derived CuCF3

Hydroxytrifluoromethylation of alkenes using the fluoroform (CF3H)-derived [CuCF3] reagent is described. In the presence of additive B2Pin2 and air, this reagent effectively facilitates the addition of hydroxy and trifluoromethyl groups across an alkene double bond, a formal hydroxytrifluoromethylation process. Various β-trifluoromethyl alcohols can be synthesized from simple alkenes where the ultimate CF3 source is the industrial byproduct fluoroform.

Five-Membered Ring Systems: Furans and Benzofurans

This review covers work published in the calendar year 2012. References to new, naturally occurring furans, dihydrofurans, and tetrahydrofurans are given. New methods for the ring synthesis of furans, dihydrofurans, and tetrahydrofurans, and benzofurans are discussed. Novel reaction chemistry of furans, dihydrofurans, and tetrahydrofurans, and benzofurans is covered.

Copper(I)-Catalyzed Interrupted Click Reaction with TMSCF3: Synthesis of 5-Trifluoromethyl 1,2,3-Triazoles

We herein describe a Cu(I)-catalyzed interrupted click reaction, using (trifluoromethyl)trimethylsilane (TMSCF3) as a nucleophilic CF3 source, to synthesize 5-trifluoromethyl 1,2,3-triazoles in one step from readily available terminal alkynes and azides. The reaction shows complete regioselectivity, broad substrate scope, and good functional group tolerability. The application of the reaction has been demonstrated in the synthesis of a trifluoromethylated analog of antiepileptic drug rufinamide.